This proposal seeks funds for the purchase of a versatile spectrophotometer system capable of measuring circular dichroism spectra (CD), as well as simultaneous measurements of absorption, CD, and fluorescence signals, as a function of time, temperature, and total concentration of added titrant. The Circular dichroism instrument, from Aviv Instruments, Inc., will incorporate a stopped flow system for rapid kinetic measurements of absorption, fluorescence, and CD at single wavelengths. This system will consist of three separately thermostatted and stepper motor-driven syringes for mixing two solutions at reproducible flow rates, the dead mixing time is less than 5 milliseconds. In addition, an automated syringe pump system will be included for automated ligand titrations. This instrument system will provide a central facility for the spectroscopic and other measurements of rapid kinetic phenomena (greater than millisecond) and conventional steady-state absorption, fluorescence, and CD spectra. This facility will benefit the research of eight user groups in the Department of Pharmaceutical Sciences and Eppley Research Institute at the University of Nebraska Medical Center. Each group includes several graduate students and postdoctoral fellows who will make heavy use of this instrumentation in their research projects. Detailed descriptions of the primary research projects which are proposed by each user group are included, as are arrangements for the management, maintenance, and organization of user groups. The research projects include (1) P- Glyprotein mediated drug transport in the blood brain barrier (W. Elmquist), (2) Regulation of non-receptor PTK activity by SH3 domains (W. Gmeiner), (3) Sequence specific DNA affinity binding (B. Gold), (4) Interactions of block copolymers in blood brain barrier (A. Kabanov), (5) Biodegradable nanospheres for drug delivery (V. Labhasetwar) (6) Thermodynamics of Nucleic acid conformation and interactions (L. A. Marky), and (7) Determinants for toxicity of calcineurin inhibitors (P. Stemmer).